Roswell Park Cancer Institute (RPCI) is an independent, free-standing research, education and clinical cancer care Institute. Dr. Donald Trump, CCSG PI and RPCI President/CEO, is responsible solely to the RPCI Board of Directors. RPCI has been continuously recognized as a Cancer Center since NCI first designated centers in 1974 and has been designated as a comprehensive center since that term was first employed. This application requests continued NCI support for another five years. RPCI occupies a 27 acre campus near downtown Buffalo. The RPCI campus consists of 1.6 million square feet (sf) of laboratory, office, clinical and education. An additional 142,000 sf clinical care, clinical research and office building began construction on April 18, 2013. New developments on the main campus since last review have included opening of the Centers for Immunotherapy, Robotic Surgery, and Personalized Medicine. An additional 16,000 sf of clinical space have been opened at three affiliate sites. While the population of the RPCI catchment area (the 8 county region of WNY from which ~86% of RPCI patients are drawn) has been generally stable at ~1.5M, the number of tumor registry cases has increased 25% since 2008. In 2012 RPCI physicians cared for 4,242 new tumor registry cases and a total of 8,626 new analytic and non-analytic cases. Since the last competitive renewal in 2008, RPCI has continued scientific, clinical, population science and education program growth, despite a difficult economic environment. This growth is demonstrated by: 1) recruitment of 137 new faculty clinicians and researchers, of which 51 are new CCSG members; 2) a 17% increase in total peer-reviewed funding from 2008 to 2013; 3) an increase in high-impact (impact factor>10) publications (91 to 193); 4) increased accrual to first-in-human, phase I, investigator-initiated studies; 24 accruals in 2008 vs 118 in 2012 and the highest phase I trial institutional recruitment in RPCI history; 5) 2.5X increase in the number of therapeutic (treatment) trials supported by peer-reviewed funding (27 to 67); and 6) opening of three new satellite RPCI facilities. RPCI has expanded its educational programs, including an international program for the training of cancer scientists, clinicians and administrators from around the world. RPCI has successfully recruited three Senior Leaders, and invested $277 million in resources for the future to build on RPCI's unique opportunities in experimental therapeutics, translational medicine, genomics and education.